Hypothesis / aims of study
β3-adrenergic receptor agonists, including mirabegron and vibegron, are frequently used as first-line drug therapy for overactive bladder (OAB) with comparable effectivity. In Japan, the use of mirabegron is contraindicated in cases of severe hepatic dysfunction, and low doses are administered to patients with estimated glomerular filtration rates (eGFR) below 30. On the other hand, the use of vibegron is not restricted in cases with renal or hepatic dysfunction. Till date, there are no reports on changes in renal and hepatic functions as a consequence of the administration of these drugs for OAB. The present study aims to investigate the same with a specific focus on assessing differences in renal function and the detailed implications in clinical practice.
Study design, materials and methods
The study included patients with newly diagnosed OAB, who were continuously prescribed either mirabegron or vibegron for at least one year in our hospital between December 2018 and December 2022. Based on OAB symptom scores (OABSS), OAB was defined as a urinary urgency (Q3) score of at least 2, and a total score of at least 3. Patients received 50 mg of either mirabegron or vibegron once daily, and were defined as the mirabegron treatment group (M-group) or the vibegron treatment group (V-group), respectively. Using blood samples, we assessed renal function by measuring creatinine (Cr) levels and eGFR. Additionally, hepatic function was evaluated by estimating levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). We retrospectively compared changes in renal and hepatic function from baseline to one year post-administration within and between the groups. Efficacy was assessed by examining changes in subjective symptoms one year post drug administration using the OABSS. Additionally, renal function groups were defined based on chronic kidney dysfunction (CKD) GFR grades: Grade 1-2 (eGFR≥60) and Grade 3 (eGFR<60). Changes in renal function and subjective symptoms (OABSS) in each drug administration group were individually examined. Patients with renal dysfunction of G4 or higher, and those who received 25 mg of mirabegron were excluded. Differences were considered statistically significant at P<0.05.
Results
A total of 245 subjects with an average age of 68.8±12.2 years were assessed. The M-group included 177 patients in (111 males, 62.7%) and the V-group included 68 patients (39 males, 57.4%), with no significant differences in age or sex (P=0.636 and P=0.466, respectively). Renal and hepatic function were not found to change significantly from baseline in both groups one year post administration of the β3-adrenergic receptor agonists (M-group, [Cr] P=0.591, [eGFR] P=0.065, [AST] P=0.833, [ALT] P=0.057; V-group: [Cr] P= 0.781, [eGFR] P=0.285, [AST] P=0.281, [ALT] P=0.389). Additionally, no significant difference in the rates of change were observed in both groups ([Cr] P=0.849, [eGFR]P=0.850, [AST]P=0.145, [ALT]P=0.063) (Table 1). In contrast, OABSS significantly improved from baseline in both groups (P<0.001), albeit, with no significant difference in the rates of change between the two groups (P=0.095) (Table 1).
Patients without renal dysfunction experienced a significant worsening of the same in the M group in comparison to baseline (P<0.001 for both Cr and eGFR). However, no significant difference in the rate of change in renal function from baseline was evident in the M group in comparison to that in V-group ([Cr] P=0.446, [eGFR] P=0.787) (Table 2). Additionally, no significant difference in the proportion of patients upgraded from G1-2 to G3 between the two groups was evident (M-group, 28.4% vs. V-group, 11.8%, P=0.062). Further, in the group without renal dysfunction, significant improvement in only Q4 (urgency urinary incontinence) was evident in the M group in comparison to that in the V group (P=0.020) (Table 2). Multivariate analysis (multiple regression analysis) using a linear regression model also demonstrated that the type of β3-adrenergic receptor agonist was an independent predictor of improvement in OABSSS-Q4 (standardized regression coefficient: 0.484, 95%CI: 0.034-0.934, P=0.035).
Interpretation of results
No significant difference in changes in renal or hepatic function was evident after treatment with either of the two β3-adrenergic receptor agonists, thus confirming the safety profile of both drugs. However, while no statistically significant differences in the percentage of patients with upgradation of renal dysfunction was observed between the two groups, more patients in the M group tended towards the same. This highlights the importance of regular follow-up of renal function post administration of mirabegron for OAB, especially in elderly and vulnerable patients. Further, even though it is beyond the scope of this study, administration of lower doses of mirabegron or other agents, including vibegron may be advisable in patients with impaired renal function or in those are expected to experience compromised renal function post treatment with mirabegron. As previously reported, in the context of OABSS, both agents were equally effective. However, in patients without renal dysfunction, mirabegron may be more efficacious than vibegron in the treatment of urgent UI. The underlying mechanisms behind this effect however, remain unclear, and warrant further investigation.